X-9891092-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_001649.4(SHROOM2):​c.433G>A​(p.Gly145Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000639 in 1,204,915 control chromosomes in the GnomAD database, including 1 homozygotes. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., 1 hem., cov: 25)
Exomes 𝑓: 0.000066 ( 1 hom. 25 hem. )

Consequence

SHROOM2
NM_001649.4 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.594
Variant links:
Genes affected
SHROOM2 (HGNC:630): (shroom family member 2) This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0075130463).
BP6
Variant X-9891092-G-A is Benign according to our data. Variant chrX-9891092-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2260387.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 25 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SHROOM2NM_001649.4 linkc.433G>A p.Gly145Ser missense_variant 3/10 ENST00000380913.8 NP_001640.1 Q13796
SHROOM2XM_005274500.5 linkc.433G>A p.Gly145Ser missense_variant 3/10 XP_005274557.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SHROOM2ENST00000380913.8 linkc.433G>A p.Gly145Ser missense_variant 3/101 NM_001649.4 ENSP00000370299.3 Q13796

Frequencies

GnomAD3 genomes
AF:
0.0000445
AC:
5
AN:
112457
Hom.:
0
Cov.:
25
AF XY:
0.0000289
AC XY:
1
AN XY:
34603
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000558
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000563
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000132
AC:
22
AN:
166204
Hom.:
0
AF XY:
0.000168
AC XY:
9
AN XY:
53660
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00147
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000408
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000659
AC:
72
AN:
1092408
Hom.:
1
Cov.:
35
AF XY:
0.0000697
AC XY:
25
AN XY:
358490
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00103
Gnomad4 SAS exome
AF:
0.0000190
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000417
Gnomad4 OTH exome
AF:
0.0000873
GnomAD4 genome
AF:
0.0000444
AC:
5
AN:
112507
Hom.:
0
Cov.:
25
AF XY:
0.0000288
AC XY:
1
AN XY:
34663
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000560
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000563
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
1
Bravo
AF:
0.0000604
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.000107
AC:
13

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 13, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.90
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
0.0020
DANN
Benign
0.50
DEOGEN2
Benign
0.012
T
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.0075
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.55
N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
1.6
N
REVEL
Benign
0.049
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0030
B
Vest4
0.067
MVP
0.36
MPC
0.073
ClinPred
0.023
T
GERP RS
-9.8
Varity_R
0.039
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150231382; hg19: chrX-9859132; COSMIC: COSV66610841; API